Tyramine excites rat subthalamic neurons in vitro by a dopamine-dependent mechanism

Abstract

Tyramine, an endogenous ligand for mammalian trace amine-associated receptors, may act as a neuromodulator that regulates neuronal activity in basal ganglia. Using whole-cell patch recordings of subthalamic nucleus (STN) neurons in rat brain slices, we found that bath application of tyramine evoked an inward current in voltage-clamp in over 60% of all STN neurons. The inward current induced by tyramine was mimicked by the D 2 -like dopamine receptor agonist quinpirole, but was only partially blocked by the D 2 -like receptor antagonist sulpiride. In contrast, the D 1 -like receptor agonist SKF38393 evoked no current in STN neurons. Inward current evoked by tyramine was significantly reduced by the catecholamine uptake inhibitor nomifensine, and by exhausting catecholamines in the brain via pre-treatment with reserpine. Tyramine also reduced the amplitude of GABA A receptor-mediated IPSCs that were evoked by focal electrical stimulation of the slice. Inhibition of IPSCs by tyramine was mimicked by quinpirole and was blocked by sulpiride but not by SCH23390, a D 1 receptor antagonist. Moreover, tyramine-induced inhibition of IPSCs was reduced in slices pre-treated with reserpine, and this inhibition could be restored by briefly superfusing the slice with dopamine. These results suggest that tyramine acts as an indirect dopamine agonist in the STN. Although inhibition of IPSCs are mediated by D 2 -like receptors, the dopaminedependent inward currents evoked by tyramine do not fit a typical dopamine receptor pharmacological profile.

Nicotine and Ethanol Activate Protein Kinase A Synergistically via Giβγ Subunits in Nucleus Accumbens/Ventral Tegmental Cocultures: The Role of Dopamine D1/D2and Adenosine A2AReceptors

“…3B). Although these antagonist concentrations are relatively high, they have been previously used in neural tissue to distinguish D 1 R from D 2 R signaling (e.g., Thomas et al, 2000;Zhu et al, 2007). These results indicate that extracellular dopamine was required for nicotine to induce CRE-mediated gene expression in cocultures of VTA and NAcb neurons.…”

A Tyramine-Gated Chloride Channel Coordinates Distinct Motor Programs of a Caenorhabditis elegans Escape Response

“…Tyramine increases chloride conductance in the Drosophila Malpighian (renal) tubules (Blumenthal, 2005). Furthermore in rats, tyramine induces strong inhibitory effects on the firing rate of caudate and cortical neurons (Henwood et al, 1979) and can induce hyperpolarization in neurons of the subthalamic nucleus (Zhu et al, 2007) of the rat brain.…”

Crystal structure of tyrosine decarboxylase and identification of key residues involved in conformational swing and substrate binding

“…Tyramine is a naturally occurring BA and has diverse applications. It could act as an endogenous ligand for mammalian trace amine-associated receptors and as a biochemical precursor for dopamine and octopamine, which are neurotransmitters and neuromodulators in invertebrate nervous systems3456. Tyramine has also been shown to be an effective therapeutic agent in Diabetes Mellitus type II by functioning as an insulin mimic to stimulate glucose transport7, and as a key intermediate of Bezafibrate for the treatment of hyperlipidemia by reducing cholesterol and triglyceride levels8.…”